Chronic Kidney Disease (CKD) can result from different causes, but the final pathway remains renal fibrosis characterized by chronic inflammation leading to abnormal accumulation of extracellular matrix (ECM). This fibrotic process leading to a decrease in the number of functioning nephrons is still not clear and constitutes the key of CKD progression. Thus, new insights into the pathophysiological mechanisms of renal fibrogenesis will guide us to a more efficient therapy. The amount of ECM is regulated by the balance between protein synthesis and degradation and it's particularly important during embryonic development and pathological states. While fibrogenesis mechanisms have been the subject of ongoing studies, attention has become focused on ECM proteins, due to their importance not only as components of fibrosis, but also as active regulators of tissue remodeling via cell-matrix signaling. In light of the foregoing, a need in the art exists for identifying a factor liable to be responsible for progression of renal fibrosis and therefore for the progression of CKD so as to envisage new tools for the treatment of such a disease.
Periostin (POSTN) also called Osteoblast-Specific Factor 2 (OSF-2) is a 90 kDa extracellular protein expressed during development and in very early postnatal tissue; its expression in healthy adult tissues is very low but increases considerably following injury.
Periostin expression has previously been shown to be significantly increased by both transforming growth factor beta-1 (TGFbeta1) and bone morphogenetic protein (BMP-2). Many studies in the heart showed that periostin is secreted by fibroblasts and regulates collagen deposition, thereby altering mechanical properties of connective tissues. When periostin was knocked out, animals showed reduced fibrosis after myocardial infarction. This matricellular protein has also the ability to associate to other ECM components as tenascin, fibronectin and to interact with integrins such as avb3 avbv, resulting in activation of Akt or PI3 kinase pathways. Recently, periostin was described in a wild range of pathologies (cancers, asthma . . . ) but little is known about periostin in the kidney, and its potential role in the progression of chronic kidney disease. To date, periostin was described in human autosomal dominant polycystic kidney and was shown to be de novo expressed in cyst epithelial cells (Wallace et al. 2008). Another study described gene expression profiles of several matricellular proteins on biopsies from patients with glomerulopathies and renal dysfunction; it showed that periostin was highly induced in tubuloibterstitial and fibrotic compartments and negatively correlated with renal function. Recently, periostin was identified in hypertensive nephropathy induced by L-NAME as an indicator of CKD progression and regression (Guerrot et al. 2012). It was indeed shown that periostin expression correlates with functional markers of kidney disease (plasma creatinine, proteinuria, renal blood flow) and that its localization was associated with perivascular fibrotic areas, hallmark of experimental hypertensive nephropathy. Interestingly, periostin was overexpressed in human kidney disease and was found in the injured fibrotic tubulointerstitial regions of chronic allograft nephropathy. Together, these results indicate that periostin is a good marker of progression and probably regression of renal fibrosis. These studies however, did not address the issue whether or not periostin participates in the development of renal fibrosis and CKD.